Substituted n-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase

A compound represented by Formula (I)

• an enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof
• wherein
• A is C3-10-cycloalkyl, 3 to 10-membered heterocycloalkyl containing 1 to 5 heteroatoms independently selected from the group consisting of N, O and S, or 6- to 10-membered mono- or bicyclic aryl, or 5 to 14-membered mono- or bicyclic heteroaryl containing 1 to 5 heteroatoms independently selected from the group consisting of N, O and S,
• wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of halogen, OH, oxo, CN, C1-6-alkyl, O—C1-6-alkyl, C(O)OR2, S(O)—C1-6-alkyl, S(O)2—C1-6-alkyl, N(R2)2, C(O)N(R2)2, S(O)2N(R2)2 and C3-6-cycloalkyl,
• wherein alkyl and cycloalkyl are unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C1-3-alkyl, OH, CN, oxo and OS(O)2CH3;
• or
• wherein two adjacent substituents complete a 3- to 8-membered saturated or partially unsaturated ring containing carbon atoms and optionally containing 1 to 3 heteroatoms selected from O, S, N, S(O), S(O)2 or NR2, wherein the ring is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of halogen, OH, oxo, CN, C1-6-alkyl, O—C1-6-alkyl, C(O)OR2, S(O)—C1-6-alkyl, S(O)2—C1-6-alkyl, N(R2)2, C(O)N(R2)2, S(O)2N(R2)2 and C3-6-cycloalkyl,
• wherein alkyl and cycloalkyl are unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C1-3-alkyl, OH, CN, oxo and OS(O)2CH3;
• R1 is hydrogen or C1-6-alkyl;
• R2 is independently selected from the group consisting of hydrogen, C1-6-alkyl, halo-C1-6-alkyl and hydroxy-C1-6-alkyl;
• Y is O or S;
• L1 is —O—, —S—, —S(O)—, —S(O)2—, or —S(O)(=NR3)—;
• R3 is hydrogen or C1-6-alkyl;
• C is a bond, C1-6-alkylene, C2-6-alkenylene, C2-6-alkynylene, C0-6-alkylene-C3-6-cycloalkylene, Co-6-alkylene-3 to 10-membered-heterocycloalkylene, C0-6-alkylene-C6-10-aryl, or C0-6-alkylene-5-to 14-membered mono- or bicyclic heteroaryl,
• wherein alkylene, alkenylene and alkynylene are unsubstituted or substituted with 1 to 3 substituents independently selected from C1-6-alkyl, halo-C1-6-alkyl, halogen, OH, OR2, N(R2)2, C3-6-cycloalkyl, and 3- to 8-membered heterocycloalkyl;
• L2 is a bond, C0-6-alkylene-NR2—C0-6-alkylene, C0-6-alkylene-O—C0-6-alkylene, C0-6-alkylene-S—C0-6-alkylene, C0-6-alkylene-S(O)—C0-6-alkylene, C0-6-alkylene-S(O)2—C0-6-alkylene, C0-6-alkylene-C(O)NR2—C0-6-alkylene, C0-6-alkylene-NR2C(O)—C0-6-alkylene, C0-6-alkylene-NR2C(=NR2)-C0-6-alkylene, C0-6-alkylene-C(═NR2)NR2—C0-6-alkylene, C0-6-alkylene-S(O)—NR2—C0-6-alkylene, C0-6-alkylene-NR2—S(O)—C0-6-alkylene, C0-6-alkylene-S(O)2—NR2—C0-6-alkylene, C0-6-alkylene-NR2—S(O)2—C0-6-alkylene, C0-6-alkylene-NR2—S(O)2—NR2—C0-6-alkylene, C0-6- alkylene-NR2-S(=NR2)(O)—C0-6-alkylene, C0-6-alkylene-NR2-0(O)-NR2—C0-6-alkylene, C0-6-alkylene-C(O)—C0-6-alkylene, C0-6-alkylene-NR2—C(O)C(O)—NR2—C0-6-alkylene, C0-6-alkylene-NR2—C(O)—CR3R4—C(O)—NR2—C0-6-alkylene, C0-6-alkylene-NR2—C(O)—CR3R4—NR2—C0-6-alkylene, C0-6-alkylene-NR2—C(O)—O—C0-6-alkylene, C0-6-alkylene-0-0(O)-NR2—C0-6-alkylene, or
• wherein alkylene may be unsubstituted or substituted with 1 to 3 substituents independently selected from C1-6-alkyl, halo-C1-6-alkyl, halogen, OH, OR2, N(R2)2, C3-6-cycloalkyl and 3- to 8-membered heterocycloalkyl,
• wherein C3-6-cycloalkyl and 3- to 8-membered heterocycloalkyl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, OH, C1-3-alkyl and halo-C1-3-alkyl;
• R4 is hydrogen, OH, N(R2)2, C1-6-alkyl, halo-C1-6-alkyl, or OH—C1-6-alkyl, or
• R3 and R4 form a 3- to 6-membered cycloalkyl ring or 3- to 6-membered heterocycloalkyl ring having 1 or 2 heteroatoms independently selected from O, N and S,
• wherein cycloalkyl and heterocycloalkyl is unsubstituted or substituted by 1 to 4 substituents independently selected from halogen or hydroxy;
• D is hydrogen, C1-6-alkyl, C1-6-fluoroalkyl, N(R2)2, C(O)OH, CN, C(O)OR2, CH(NH2)C(O)OH, S(O)2C1-6-alkyl, S(O)C1-6-alkyl, S(O)2N(R2)2, NR2S(O)2N(R2)2, NR2S(O)2C1-6-alkyl, C(O)N(R2)2, S(O)(═NR2)C1-6-alkyl, C3-6 cycloalkyl, 4- to 8-membered mono- or bicyclic heterocycloalkyl containing 1, 2 or 3 heteroatoms independently selected from the group consisting of O, S and N, C6-10-aryl, or 5- to 10-membered mono- or bicyclic heteroaryl containing 1, 2, 3 or 4 heteroatoms selected from O, S and N,
• wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of halogen, OH, oxo, CN, C1-6-alkyl, halo-C1-6-alkyl, hydroxy-C1-6-alkyl, O—C1-6-alkyl, C0-6-alkylene-C(O)OR2, S(O)—C1-6-alkyl, S(O)2—C1-6-alkyl, N(R2)2, C(O)N(R2)2, S(O)2N(R2)2, NR2S(O)2NR2, C3-6-cycloalkyl, 3- to 6-membered heterocycloalkyl, S(O)(═NR2)R2, S(O)(═NR2)N(R2)2 and heteroaryl
• wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of halogen, OH, CN, NH2, oxo and OS(O)2CH3;
• with the proviso that
• (a) when L2 represents —O— then D is not S(O)2N(R2)2, and
• (b) when C represents a bond then D is not hydrogen.